Atallah F. Ahmed

Five novel norcembranoids from Sinularia leptoclados and S. parva

Abstract Three new norcembrane-based diterpenoids, leptocladolides A ( 1 ), B ( 4 ) and C ( 5 ), along with five known metabolites 6 – 10 , have been isolated from the dichloromethane extract of a Taiwanese soft coral Sinularia leptoclados . Furthermore, a chemical investigation on the dichloromethane extract of S. parva has resulted in the isolation of two new related isomers, 1- epi -leptocladolide A ( 2 ) and 7 E -leptocladolide A ( 3 ), in addition to 1 and 7 . The structures of new metabolites 1 – 5 were elucidated on the basis of extensive spectroscopic analyses and their relative stereochemistries were determined by NOESY experiments. The new metabolites 1 and 3 have been shown to exhibit significant cytotoxic activity against KB and Hepa59T/VGH cancer cell lines.

A C-3 methylated isocembranoid and 10-oxocembranoids from a formosan soft coral, Sinularia grandilobata.

Five new cembranoids, designated grandilobatins A-E (1- 5), were isolated from the soft coral Sinularia grandilobata. Grandilobatin C (3) was found to have a novel skeleton with the C-4 methyl group of the normal cembranoid rearranged to C-3, while the other metabolites were identified as new 10-oxocembranoids. Metabolite 4 has weak cytotoxicity toward MDA-MB-23 human breast tumor cells. Also, 4 significantly inhibited the accumulation of the pro-inflammatory iNOS protein of LPS-stimulated RAW264.7 macrophage cells at 50 microM.

Oxygenated cembranoids from a Formosan soft coral Sinularia gibberosa.

Chemical investigation of a Formosan soft coral, Sinularia gibberosa, has led to the isolation of eight oxygenated cembranoids, 1- 8, including seven new compounds, gibberosenes A-G ( 2- 8). None of these compounds were found to be cytotoxic toward a limited panel of cancer cell lines. Compound 1 significantly inhibited the accumulation of the pro-inflammatory COX-2 protein of the LPS-stimulated RAW264.7 macrophage cells.

1α,3β,5β-Trihydroxy-24-methylenecholestan-6-one: a novel steroid from a soft coral Sinularia gibberosa

A novel steroid, 1α,3β,5β-trihydroxy-24-methylenecholestan-6-one (gibberoketosterol) (1), along with four known steroids, was isolated from the lipophilic extracts of a Taiwanese soft coral Sinularia gibberosa. The structure of the new metabolite was determined on the basis of extensive spectral analyses and chemical reaction. The relative stereochemistry of gibberoketosterol was established by the NOESY experiments and analysis of the pyridine-induced deshielding effect of the axial hydroxy groups. Gibberoketosterol is the first example of 1α,3β,5β-trihydroxy-6-oxosteroids isolated from natural sources and was found to exhibit a moderate cytotoxicity against the growth of Hepa59T/VGH cancer cells.

Sinugrandisterols A-D, trihydroxysteroids from the soft coral Sinularia grandilobata

Four new trihydroxysteroids, sinugrandisterols A-D (1-4), have been isolated from the CH(2)Cl(2)-soluble fraction of the EtOH extract of Sinularia grandilobata. The structures of these metabolites were determined on the basis of spectroscopic (IR, MS, and 1D and 2D NMR) analysis. The cytotoxicity of 1-4 toward a limited panel of cancer cell lines is also reported.

Klyflaccicembranols A-I, New Cembranoids from the Soft Coral Klyxum flaccidum.

New cembranoids klyflaccicembranols A–I (1–9), along with gibberosene D (10), have been isolated from the organic extract of a Formosan soft coral Klyxum flaccidum. Their structures were established by extensive spectroscopic analyses, including 2D NMR spectroscopy, and spectral data comparison with related structures. The cytotoxicity of the isolated metabolites, as well as their nitric oxide (NO) inhibitory activity, were evaluated and reported. Metabolites 2, 4, 6, 8 and 9 were found to exhibit variable activities against a limited panel of cancer cell lines in a range of IC50 16.5–49.4 μM. Among the tested cembranoids, compounds 4, 5, 6, and 9 significantly inhibited NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages at a dose of 50 μg/mL.

Anti-Inflammatory Lobane and Prenyleudesmane Diterpenoids from the Soft Coral Lobophytum varium

New lobane-based diterpenoids lobovarols A–D (1–4) and a prenyleudesmane-type diterpenoid lobovarol E (5) along with seven known related diterpenoids (6–12) were isolated from the ethyl acetate extract of a Taiwanese soft coral Lobophytum varium. Their structures were identified on the basis of multiple spectroscopic analyses and spectral comparison. The absolute configuration at C-16 of the known compound 11 is reported herein for the first time. The anti-inflammatory activities of compounds 1–12 were assessed by measuring their inhibitory effect on N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils. Metabolites 2, 5, and 11 were found to show moderate inhibitory activity on the generation of superoxide anion, while compounds 5, 8, 11, and 12 could effectively suppress elastase release in fMLP/CB-stimulated human neutrophil cells at 10 μM. All of the isolated diterpenoids did not exhibit cytotoxic activity (IC50 > 50 μM) towards a limited panel of cancer cell lines.

Anti-Inflammatory Polyoxygenated Steroids from the Soft Coral Lobophytum michaelae

Three new polyoxygenated steroids, michosterols A–C (1–3), and four known compounds (4–7) were isolated from the ethyl acetate (EtOAc) extract of the soft coral Lobophytum michaelae, collected off the coast of Taitung. The structures of the new compounds were elucidated on the basis of spectroscopic analyses and comparison of the nuclear magnetic resonance (NMR) data with related steroids. The cytotoxicity of compounds 1–3 against the proliferation of a limited panel of cancer cell lines was assayed. Compound 1 was found to display moderate cytotoxicity against adenocarcinomic human alveolar basal epithelial (A549) cancer cells. It also exhibited potent anti-inflammatory activity by suppressing superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-stimulated human neutrophils. Furthermore, 3 could effectively inhibit elastase release, as well.

Isolation and Structure Elucidation of Cembranoids from a Dongsha Atoll Soft Coral Sarcophyton stellatum

Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A–C (1–3), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (7–16) from the ethyl acetate (EtOAc) extract of soft coral Sarcophyton stellatum. The structures of the new compounds were established by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and data comparison with related structures. Compounds 8 and 14 were isolated from a natural source for the first time. The isolated metabolites were shown to be not cytotoxic against a limited panel of cancer cells. Compound 9 showed anti-inflammatory activity by reducing the expression of proinflammatory cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins in lipopolysaccharide (LPS)-stimulated mouse leukaemic monocyte macrophage (RAW 264.7) cells.

New Cembranoids and a Biscembranoid Peroxide from the Soft Coral Sarcophyton cherbonnieri

Six new cembranoids, cherbonolides A−E (1–5) and bischerbolide peroxide (6), along with one known cembranoid, isosarcophine (7), were isolated from the Formosan soft coral Sarcophyton cherbonnieri. The structures of these compounds were elucidated by detailed spectroscopic analysis and chemical methods. Compound 6 was discovered to be the first example of a molecular skeleton formed from two cembranoids connected by a peroxide group. Compounds 1–7 were shown to have the ability of inhibiting the production of superoxide anions and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophils.